The lung is a major target for opportunistic infections in human immunodeficiency virus (HIV)-seropositive patients. HIV and cytomegalovirus (CMV) can be detected in lung tissues in vivo. Moreover, both HIV and CMV cause substantial immunosuppression that is mediated, in part, by the proinflammatory cytokines. A fundamental concept has emerged: the relative amounts of the proinflammatory cytokines, their anatagonists, and the relevant chemokines that are produced during infection or inflammation, influence the pathogenesis, resolution or progression of disease. Little is known about cytokine antagonist or chemokine production in the lung or the influence of CMV coinfection on these factors. Our major hypothesis is that CMV infection of lung tissue and the balance between proinflammatory cytokines, naturally-occurring cytokine antagonists and chemokines determine the amount of HIV replication in the lung and the degree of alveolar macrophages (AM) and CD8 cytotoxic T Lymphocyte (CTL) dysfunction. We will test this hypothesis using AM obtained from patients at all stages of HIV-related disease, some of whom will have CMV infection (either latent or active). We will measure the levels of proinflammatory cytokines, cytokine antagonists, and chemokines (MIP-1a, MIP-1b, and RANTES); the amount of HIV and CMV in lung tissue as compared to plasma and peripheral blood; the changes in proliferative response of AM to mitogens and antigens; and alteration in lung CD8 CTL function.